CONICET Digital

Statistical thermodynamics of adsorbates with nonsymmetrical lateral interactions

Statistical thermodynamics of adsorbates with nonsymmetrical lateral interactions Romá, Federico José; Ramirez Pastor, Antonio Jose The exact adsorption thermodynamics of particles with nonsymmetrical ad-ad interactions on a one-dimensional space is presented. The asymmetry is introduced by considering the lateral interactions depending on the orientation of the adsorbed molecules. The adsorption process is monitored by following the adsorption isotherm, the thermodynamic factor, the differential heat of adsorption, and the configurational entropy of the adlayer. A rich variety of different behaviors is found with respect to the standard lattice gas of interacting monomers. The resulting thermodynamic description may also be applicable to adsorption and transport of nonspherical molecules in low-dimensional systems such as carbon nanotubes.

Neural cell adhesion molecule in human serum. Increased levels in dementia of the Alzheimer type

Neural cell adhesion molecule in human serum. Increased levels in dementia of the Alzheimer type Todaro, Laura Beatriz; Puricelli, Lydia Ines; Gioseffi, Hernan; Pallotta, María Guadalupe; Lastiri, José; Bal de Kier Joffe, Elisa; Varela, Mirta; Sacerdote de Lustig, Eugenia Memory impairment is a process associated with alterations in neuronal plasticity, synapses formation, and stabilization. As the neural cell adhesion molecule (NCAM) plays a key role in synaptic bond stabilization, we analyzed the usefulness of soluble NCAM isoforms in the diagnosis of patients with dementia of the Alzheimer type (DAT). NCAM was measured in the sera of 70 control subjects and 43 DAT patients (with different severity of cognitive impairment, GDS), employing Western blot and densitometric quantification. LMW-NCAM bands (100–130 kDa) decreased significantly with age independently of sex. DAT patients presented values of LMW-NCAM and HMW-NCAM significantly higher than healthy controls of similar age (higher than 130 kDa). Only LMW-NCAM was associated with GDS. Our results suggest that NCAM could be involved in the pathogenesis of DAT disorder and that serum NCAM levels could be useful as differential diagnostic markers of the disease.

Dose-dependent activity of albendazole against benzimidazole-resistant nematodes in sheep: relationship between pharmacokinetics and efficacy

Dose-dependent activity of albendazole against benzimidazole-resistant nematodes in sheep: relationship between pharmacokinetics and efficacy Moreno Torrejon, Laura; Echevarria, Flavio A. M.; Muñoz, Fabio; Alvarez, Luis Ignacio; Sanchez Bruni, Sergio Fabian; Lanusse, Carlos Edmundo The relationship between the pharmacokinetic behaviour and the anthelmintic efficacy of albendazole (ABZ) against benzimidazole (BZD)-resistant nematodes was studied in sheep. A micronized ABZ suspension was orally administered at two different dose levels to sheep naturally infected with BZD-resistant gastrointestinal (GI) nematodes. The experimental animals were allocated into the following groups (n=8): (a) untreated control; (b) orally treated with ABZ at 3.8 mg/kg b.w.; and (c) orally treated with ABZ at 7.5 mg/kg b.w. Plasma samples were obtained serially over 72 h post-treatment from both treated groups and analysed by HPLC to measure the concentrations of ABZ and its sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites. Faecal egg counts were performed prior to treatment and at the necropsy day. All experimental animals were sacrificed 10 days after treatment to perform GI worm counts. While ABZ parent drug was not recovered in the bloodstream, ABZSO and ABZSO2 were the molecules found in plasma. ABZSO was the metabolite measured at the highest concentrations in the bloodstream for up to 36 (treatment at 3.8 mg/kg) or 60 h (treatment at 7.5 mg/kg) post-administration. There was a proportional relationship between the administered ABZ dose and the measured plasma concentrations of both ABZ metabolites. Over a 100% increment on the plasma AUC values for the anthelmintically active ABZSO metabolite was observed at the 7.5 mg/kg compared to the 3.8 mg/kg treatment. The low efficacy patterns (<24%) observed against the GI nematodes investigated indicate a high level of resistance to ABZ given at 3.8 mg/kg an efficacious therapeutic dose rate recommended in some countries. However, the higher and prolonged plasma drug concentration measured after the 7.5 mg/kg treatment resulted in an improved efficacy pattern (estimated by both faecal egg and adult worm counts) against most of the GI nematodes studied compared to that obtained at the lower dose rate. A direct relationship between drug pharmacokinetic behaviour and anthelmintic efficacy against BZD-resistant nematodes in sheep was shown in the current work, although individual variation precluded the observation of statistically significant differences in worm counts.

Surface characterization of reprocessed single-use medical catheters by fractal mass dimension

Surface characterization of reprocessed single-use medical catheters by fractal mass dimension Scandurra, Adriana Gabriela; Arizmendi, Constancio Miguel; Cuadrado, Teresita Raquel; Granados, Dolly Lucía Reprocessing of single-use medical devices is an issue of concern and discussion due to infection risk and operation failure. Cleaning procedures and sterilization processes can produce structural changes and relevant topographical alteration of the biomedical device surfaces which may activate mechanisms able to cause unwanted biological response. Atomic Force Microscopy analysis (AFM) to measure Poly(vinyl chloride) (PVC) catheters surface roughness variation along successive sterilization cycles was applied. In this work, the relation between the number of reprocessing cycles and the fractal mass dimension of reprocessed catheter surface microscopic images is studied.

Influence of hay quality and pasture location on performance of beef cattle grazing oats

Influence of hay quality and pasture location on performance of beef cattle grazing oats; Influencia de la calidad del heno suplementario y la localización de la pastura sobre el rendimiento de bovinos de carne a pastoreo sobre avena Arelovich, Hugo Mario; Laborde, Hugo Eduardo; Arzadún, M. J.; Vasquez, Maria Gabriela Heifers grazing oat pasture (OP) at two locations in Argentina, Argerich (ARG) and Pasman (PAS), were subjected to one of three different dietary supplement treatments: (1) control (CON, no supplement), (2) sorghum hay (SH), or (3) alfalfa-grass hay (AGH), all provided ad libitum in individual pens. The variables measured were: dry matter (DM) yield and composition of OP, hay intake, average daily weight gain (ADG), rumen pH and NH3-N, and blood mineral levels. DM availability did not limit OP intake. OP crude protein (CP) content ranged from 11.3 to 13% at ARG, and 10.7 to 13.3% at PAS. OP-minerals varied with location; the mean K/(Ca + Mg) ratios were 5.68 meq (ARG) and 4.82 meq (PAS). Heifers ate more AGH (785 g) than SH (684 g; P = 0.08). Hay consumption was 2.88 times greater at PAS than at ARG (P < 0.05). ADG was larger with SH (558 g) and AGH 594 g than with CON treatment (454 g); the average for ARG animals was 571 g compared to 500 g for PAS animals (P <0.05). Rumen pH was lower at 14:30 h (pH 6.7) than at 10:00 h (pH 7.5; P < 0.05). NH3-N values were higher at 14:30 h (19.59 mg dl-1) than at 10:00 h (4.69 mg dl-1; P < 0.05). Plasma Ca (15.50 mg dl–1) and Mg (2.84 mg dl–1) levels were higher in PAS cattle (P < 0.05). Animal performance improved with hay supplementation, but location affected response intensity.; Se realizaron tres tratamientos con novillas pastoreando verdeos de avena (VA) en dos localidades de Argentina, Argerich (ARG) y Pasman (PAS): (1) Control (CON, sin suplemento), (2) heno de sorgo (HS), y (3) heno de alfalfa y gramíneas (HAG), suplementados ad libitum en corrales individuales. Evaluamos rendimiento de materia seca (MS) y composición en VA; y en los animales consumo del heno, ganancia diaria de peso (GDP), pH y N-NH3 en rumen, y minerales en sangre. La disponibilidad de MS no limitó el consumo de VA; su proteína bruta (PB) osciló entre 11,3 y 13% (ARG), 10,7 y 13.3% (PAS). Los minerales en VA variaron entre localidades, la relación K/(Ca + Mg) promedió 5,68 meq (ARG) y 4,82 meq (PAS). Las novillas consumieron diariamente más HAG (785 g) que HS (684 g; P = 0.08), y 2,88 veces más heno en PAS que en ARG (P < 0,05). En GDP, HS (558 g) y HAG (594 g) superaron al CON (454 g), y la media de ARG (571 g) a PAS (500 g; P < 0,05). En el rumen el pH decreció a las 14:30 h (6,7) vs. 10:00 h (7,5; P < 0,05), y el N-NH3 (mg dl-1) aumentó a las 14:30 h (19,59) vs. 10:00 h (4,69; P < 0,05). Ca (15.50 mg dl–1) y Mg (2.84 mg dl–1) en plasma fue mayor en PAS (P < 0,05). El rendimiento animal mejoró con la suplementación, pero la magnitud de respuesta estuvo afectada por la localidad.

Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection: a potential mechanism of tumor-immune privilege

Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection: a potential mechanism of tumor-immune privilege Rubinstein, Natalia; Alvarez, Mariano; Zwirner, Norberto Walter; Toscano, Marta Alicia; Ilarregui, Juan Martin; Bravo, Alicia; Jose Mordoh; Leonardo Fainboim; Podhajcer, Osvaldo Luis; Rabinovich, Gabriel Adrián Despite the existence of tumor-specific immune cells, most tumors have devised strategies to avoid immune attack. We demonstrate here that galectin-1 (Gal-1), a negative regulator of T cell activation and survival, plays a pivotal role in promoting escape from T cell-dependent immunity, thus conferring immune privilege to tumor cells. Blockade of immunosuppressive Gal-1 in vivo promotes tumor rejection and stimulates the generation of a tumor-specific T cell-mediated response in syngeneic mice, which are then able to resist subsequent challenge with wild-type Gal-1-sufficient tumors. Our data indicate that Gal-1 signaling in activated T cells constitutes an important mechanism of tumor-immune escape and that blockade of this inhibitory signal can allow for and potentiate effective immune responses against tumor cells, with profound implications for cancer immunotherapy

Supplement to the paper “Packed Bed Photocatalytic Reactors . A Packing Structure Model and its Experimental Validation with Computerized Tomography

Supplement to the paper “Packed Bed Photocatalytic Reactors . A Packing Structure Model and its Experimental Validation with Computerized Tomography Irazoqui, Horacio Antonio; Isla, Miguel Angel; Brandi, Rodolfo Juan The radiation field in photocatalytic packed beds results from direct energy exchange between the lamp and the catalytic beads, and from mutual exchange between beads that are close to each other. The statistical description of these exchange mechanisms requires of the knowledge of the one-particle and two-particle distribution functions. The detailed physical and mathematical basis of a statistical model of the structure of a bed of spherical-like particles of non-negligible diameter, are presented in this supplement. The proposed model has been cast in terms of one and two-particle distribution functions, based on a widely accepted physical picture of the packing structure. The model reproduces the expected bed structure surrounding arbitrarily chosen particles at different distances from the annulus walls. Elsewhere [9], this theoretical model has been validated against results obtained with tomography experiments.

Vibrational spectra of Cd2As2O7

Vibrational spectra of Cd2As2O7 Baran, Enrique José; Weil, Matthias The infrared and Raman spectra of Cd2As2O7, belonging to the thortveitite structural type, were recorded and are discussed on the basis of a factor group analysis and by comparisons with related compounds.

Nitric oxide, complex I, and the modulation of mitochondrial reactive species in biology and disease

Nitric oxide, complex I, and the modulation of mitochondrial reactive species in biology and disease Carreras, Maria Cecilia; Franco, María Clara; Peralta, Jorge Guillermo; Poderoso, Juan José Mitochondria are the specialized organelles for energy metabolism but also participate in the production of O2 active species, cell cycle regulation, apoptosis and thermogenesis. Classically, regulation of mitochondrial energy functions was based on the ADP/ATP ratio, which dynamically stimulates the transition between resting and maximal O2 uptake. However, in the last years, NO was identified as a physiologic regulator of electron transfer and ATP synthesis by inhibiting cytochrome oxidase. Additionally, NO stimulates the mitochondrial production of O 2 active species, primarily O2- and H 2O2, and, depending on NO matrix concentration, of ONOO-, which is responsible for the nitrosylation and nitration of mitochondrial components. By this means, alteration in mitochondrial complexes restricts energy output, further increases O2 active species and changes cell signaling for proliferation and apoptosis through redox effects on specific pathways. These mechanisms are prototypically operating in prevalent generalized diseases like sepsis with multiorgan failure or limited neurodegenerative disorders like Parkinson's disease. Complex I appears to be highly susceptible to ONOO- effects and nitration, which defines an acquired group of mitochondrial disorders, in addition to the genetically induced syndromes. Increase of mitochondrial NO may follow over-expression of nNOS, induction and translocation of iNOS, and activation and/or increased content of the newly described mtNOS. Likewise, mtNOS is important in the modulation of O2 uptake and cell signaling, and in mitochondrial pathology, including the effects of aging, dystrophin deficiency, hypoxia, inflammation and cancer.

In vitro effect of gamma-aminobutyric acid on bovine spermatozoa capacitation

In vitro effect of gamma-aminobutyric acid on bovine spermatozoa capacitation Ritta, Monica Nora; Bas, Diana Ester; Tartaglione, C. M. Sperm capacitation is defined as the maturational changes that render a sperm competent for fertilization and occurs in the female reproductive tract. Identification of the factor/s that regulate sperm capacitation would allow the understanding of these phenomena. Among these factors, gamma-aminobutyric acid (GABA) has recently become as a putative modulator of sperm function. The aim of this study was to explore the presence of a GABAergic regulation of bovine sperm capacitation as well as the possible intracellular mechanisms involved. GABA was detected in fresh semen by a sensitive radioreceptor assay (spermatozoa, 0.064 +/- 0.003 nmoles/10(6) cells; seminal plasma, 23.21 +/- 1.16 nmoles/ml). Scatchard analysis of [(3)H]-muscimol binding to sperm membranes yielded a linear plot consistent with a single population of binding sites (K(d) = 3.87 nM, B(max) = 417 fmol/mg prot.). [(3)H]-muscimol specific binding to sperm membranes was significantly inhibited by the GABA A receptor (GABA A-R) antagonist bicuculline and by the agonists muscimol and isoguvacine. Addition of GABA to the incubation medium resulted in a concentration-dependent increase in the percentage of capacitated spermatozoa (chlortetracycline assay). We observed a significant increment on intracellular calcium and cyclic 3',5' adenosine monophosphate (cAMP) concentrations induced by GABA, being the cation influx abolished when the cell suspensions were coincubated with the antagonists bicuculline or picrotoxin. It is concluded that GABA induces sperm capacitation through an intracellular mechanism dependent on calcium influx and cAMP accumulation mediated by a specific GABA A-R.

Anterior hypothalamic β-adrenergic activity in the maintenance of hypertension in aortic coarctated rats

Anterior hypothalamic β-adrenergic activity in the maintenance of hypertension in aortic coarctated rats Höcht, Christian; Opezzo, Javier A. W.; Taira, Carlos Alberto The aim of this work was to demonstrate an alteration of the anterior hypothalamic catecholaminergic system in aortic coarctated (ACo) rats by the perfusion of β-adrenergic antagonist and the microinfusion of β-adrenergic agonist. Wistar urethane-chloralose anesthetized rats were used. The carotid artery was cannulated for blood pressure recording and changes in blood pressure were measured. A concentric microdialysis probe was inserted in the anterior hypothalamus. Metoprolol (a β1- adrenoceptor antagonist) perfusion (6μgml-1) reduced the mean arterial pressure (MAP) in the ACo rats but not in sham operated (SO) animals. The anterior hypothalamic infusion of non-specific β-adrenergic agonist isoproterenol induced a dose-dependent decrease of blood pressure in both experimental groups, but the depressor response was significantly lower in ACo rats. The pretreatment with atenolol, a selective β1- adrenoceptor antagonist, increased the depressor effect of isoproterenol in ACo rats, but not in SO rats. On the other hand, the hypotensive action of isoproterenol was significantly diminished after the administration of non-specific β-adrenoceptor antagonist propranolol in SO and ACo rats. The anterior hypothalamic infusion of clenbuterol, a selective β 2-adrenergic agonist, induced a dose-dependent decrease of blood pressure in both experimental groups. The depressor response to clenbuterol (1nmol) was significantly lower in ACo rats than in SO rats. In summary, this study provides the evidence that there is a β1-adrenergic compromise in anaesthetized ACo rats and this compromise may be involved in the maintenance of hypertension. On the other hand, this study also suggests the existence of pressor β1-adrenoceptors in the anterior hypothalamic area of ACo rats but not in SO rats. We also found a diminished depressor β2-adrenergic activity in ACo rats.

Early juvenile pterosaurs (Pterodactyloidea: Pterodaustro guinazui) from the Lower Cretaceous of central Argentina

Early juvenile pterosaurs (Pterodactyloidea: Pterodaustro guinazui) from the Lower Cretaceous of central Argentina Codorniú Dominguez, Laura Susana; Chiappe, Luis We report on two juvenile specimens of Pterodaustro guinazui, a medium-sized, filter-feeding pterodactyloid pterosaur from the Lower Cretaceous (Albian) lacustrine deposits of the Lagarcito Formation of central Argentina (Sierra de Las Quijadas, San Luis Province). Both specimens lack the skull, but one is otherwise nearly complete and articulated, and the other is more fragmentary. Their small size (~300 mm of wingspan), the lack of fusion of several postcranial bones, the minimal epiphyseal ossification, and the porous appearance of the periosteal surfaces indicate the specimens died at a very early stage of postnatal development. The presence of derived characters unique, within Pterodactyloidea, to P. guinazui (e.g., caudal vertebrae exceeding 16 elements) supports the proposed specific identification of the specimens. The new material provides anatomical information previously unknown for P. guinazui and sheds light on allometric transformations during the growth of this pterosaur. Comparisons with more mature and much larger individuals support two major allometric trends: (i) the negative allometric growth of the proximal portion of the forelimb, and (ii) the positive allometric growth of the metacarpal IV.; Nous soumettons un article sur deux spécimens juvéniles de Pterodaustro guinazui, un ptérosaurien ptérodactyloidé, de taille moyenne et qui se nourrit par filtrage, dans les dépôts lacustres de la Formation de Lagarcito (Crétacé inférieur – Albien) du centre de l'Argentine (Sierra de Las Quijadas, province de San Luis). Aucun des deux spécimens n'a de crâne mais l'un des deux est presque complet et articulé alors que l'autre est plus fragmenté. Leur petite taille (envergure ~ 300 mm), le manque de fusion de plusieurs os postcrâniens, l'ossification épiphysaire minimale et l'apparence poreuse des surfaces du périoste indiquent que les spécimens sont morts à un stage très précoce de développement postnatal. La présence de caractères dérivés, uniques à Pterodaustro guinazui chez les ptérodactylidés, (p. ex. des vertèbres caudales à plus de 16 éléments) supporte l'identification spécifique proposée des spécimens. Le nouveau matériel fournit de l'information anatomique auparavant inconnue pour Pterodaustro guinazui et nous renseigne sur les transformations allométriques au cours de la croissance de ce ptérosaurien. Des comparaisons avec des individus plus adultes et beaucoup plus grands supportent deux tendances allométriques majeures : (1) la croissance allométrique négative de la portion proximale du membre antérieur et (2) la croissance allométrique positive du 4e métacarpien.

Calculation of the pressure dependence of the bulk modulus using a jellium model

Calculation of the pressure dependence of the bulk modulus using a jellium model Fernández, G. E.; Serebrinsky, Santiago Ariel; Gervasoni, Juana Luisa; Abriata, Jose Pablo We evaluate the electronic contribution to the pressure dependence of the bulk modulus B of pure metals using an effective jellium model to characterize the electronic density. The partial derivative n = ∂B/∂P evaluated at zero pressure (and at constant temperature) is the main parameter on which the Murnaghan equation of state depends. The general features of this method are discussed and the corresponding results are compared with experimental data.

Pifithrin-alpha inhibits p53 signaling after interaction of the tumor suppressor protein with hsp90 and its nuclear translocation

Pifithrin-alpha inhibits p53 signaling after interaction of the tumor suppressor protein with hsp90 and its nuclear translocation Murphy, Patrick J.; Galigniana, Mario Daniel; Morishima, Yoshihiro; Harrell, Jennifer M.; Kwok, Roland P.; Ljungman, Mats; Pratt, William B. Pifithrin-alpha (PFTalpha) was originally thought to be a specific inhibitor of signaling by the tumor suppressor protein p53. However, the laboratory that discovered pifithrin recently reported that the compound also inhibits heat shock and glucocorticoid receptor (GR) signaling, and they suggested that PFTalpha targets a factor common to all three signal transduction pathways, such as the hsp90/hsp70-based chaperone machinery (Komarova, E. A., Neznanov, N., Komarov, P. G., Chernov, M. V., Wang, K., and Gudkov, A. V. (2003) J. Biol. Chem. 278, 15465-15468). Because it is important for the mechanistic study of this machinery to identify unique inhibitors of chaperone action, we have examined the effect of PFTalpha on transcriptional activation, the hsp90 heterocomplex assembly, and hsp90-dependent nuclear translocation for both p53 and the GR. At concentrations where PFTalpha blocks p53-mediated induction of p21/Waf-1 in human embryonic kidney cells, we observed no inhibition of GR-mediated induction of a chloramphenicol acetyl transferase reporter in LMCAT cells. PFTalpha did, however, cause a left shift in the dexamethasone dose response curve by increasing intracellular dexamethasone concentration, apparently by competing for dexamethasone efflux from the cell. The assembly of p53 or GR heterocomplexes with hsp90 and immunophilins was not affected by PFTalpha either in vivo or in vitro and did not affect the nuclear translocation of either transcription factor. Thus, we conclude that PFTalpha does not inhibit GR-mediated induction or the function of the chaperone machinery, and, as originally thought, it may specifically inhibit p53 signaling by acting at a stage after p53 translocation to the nucleus.

Shedding light on the immunomodulatory properties of galectins: novel regulators of innate and adaptive immune responses

Shedding light on the immunomodulatory properties of galectins: novel regulators of innate and adaptive immune responses Rabinovich, Gabriel Adrián; Toscano, Marta Alicia; Ilarregui, Juan Martin; Rubinstein, Natalia Galectins are a large family of structurally related beta-galactoside-binding proteins that play a pivotal role in the control of cell differentiation, proliferation, activation and apoptosis of many different cell types including immune cells. By crosslinking specific glycoconjugates, different members of the galectin family behave as pro-inflammatory or anti-inflammatory "cytokine-like" mediators, acting at different levels of innate and adaptive immune responses. Here we will review recent advances on the role of galectins in key events of the immune and inflammatory response, such as tolerance induction, cell cycle progression, cell adhesion, chemotaxis, antigen presentation and apoptosis. In particular we will examine the influence of individual members of the galectin family in the physiology of different immune cell types involved in innate and adaptive immune responses. Moreover, we will discuss the importance of these sugar-binding proteins as therapeutic targets in Th1- and Th2-mediated immune disorders, an exciting area for future research.

The role of galectins in the initiation, amplification and resolution of the inflammatory response

The role of galectins in the initiation, amplification and resolution of the inflammatory response Rubinstein, Natalia; Ilarregui, Juan Martin; Toscano, Marta Alicia; Rabinovich, Gabriel Adrián Inflammation involves the sequential activation of signalling pathways leading to the production of both pro-inflammatory and anti-inflammatory mediators. Galectins constitute a family of structurally related beta-galactoside-binding proteins, which are defined by their affinity for poly-N-acetyllactosamine-enriched glycoconjugates and sequence similarities in the carbohydrate recognition domain. By crosslinking specific glycoconjugates, different members of the galectin family behave as pro-inflammatory or anti-inflammatory agents, acting at different levels of acute and chronic inflammatory responses. Recent studies highlighted immunomodulatory roles for galectins in vivo in several experimental models of chronic inflammation, suggesting that these carbohydrate-binding proteins may be potential targets for the design of a novel generation of anti-inflammatory agents. In this study, we review recent advances on the role of galectins in the initiation, amplification and resolution of the inflammatory response. In particular, we examine the influence of individual members of this family in regulating cell adhesion, migration, chemotaxis, antigen presentation, immune cell activation and apoptosis. From a better understanding of the molecular basis of galectin-induced immune regulation, we may become able to exploit the potential of these sugar-binding proteins and their glycoligands as suitable therapeutic agents in acute and chronic inflammatory disorders.

Mepyramine, a histamine H1 receptor inverse agonist, binds preferentially to a G protein-coupled form of the receptor and sequesters G protein

Mepyramine, a histamine H1 receptor inverse agonist, binds preferentially to a G protein-coupled form of the receptor and sequesters G protein Fitzsimons, Carlos P.; Monczor, Federico; Fernandez, Natalia Cristina; Shayo, Carina Claudia; Davio, Carlos Alberto Accurate characterization of the molecular mechanisms of the action of ligands is an extremely important issue for their appropriate research, pharmacological, and therapeutic uses. In view of this fact, the aim of the present work was to investigate the mechanisms involved in the actions of mepyramine at the guinea pig H(1) receptor stably expressed in Chinese hamster ovary cells. We found that mepyramine is able to decrease the basal constitutive activity of the guinea pig H(1) receptor, to bind with high affinity to a G(q/11) protein-coupled form of the receptor and to promote a G protein-coupled inactive state of the H(1) receptor that interferes with the G(q/11)-mediated signaling of the endogenously expressed ATP receptor, as predicted by the Cubic Ternary Complex Model of receptor occupancy. The effect of mepyramine on ATP-induced signaling was specifically neutralized by Galpha(11) overexpression, indicating that mepyramine is able to reduce G protein availability for other non-related receptors associated with the same signaling pathway. Finally, we found a loss of mepyramine efficacy in decreasing basal levels of intracellular calcium at high Galpha(11) expression levels, which can be theoretically explained in terms of high H(1) receptor constitutive activity. The whole of the present work sheds new light on H(1) receptor pharmacology and the mechanisms H(1) receptor inverse agonists could use to exert their observed negative efficacy.

Hodenmastzellen und männliche Infertilität

Hodenmastzellen und männliche Infertilität; Testicular mast cells and male infertility. Mayerhofer, Artur; Meineke, V.; Weidinger, S.; Köhn, F. M.; Frungieri, Monica Beatriz Die Fibrose der Wand der Samenkanälchen ist eine seit langem bekannte typische Veränderung bei Männern mit Spermatogenesedefekten, deren Ursache und deren direkte Konsequenz aber nicht bekannt sind. Da im Hoden von Männern mit Spermatogenesestörungen deutlich vermehrt Mastzellen vorkommen, von denen viele aktiviert und degranuliert sind, ist zu erwarten, daß Produkte der Mastzellen freigesetzt werden. Wir stellen die Hypothese auf, daß sie an der Entstehung der Tubulusfibrose und der Spermatogenesestörung beteiligt sind. Untersuchungen in menschlichen Zellkulturen zeigten, daß Tryptase, das Hauptprodukt der Mastzellen, die Bildung von COX-2 und von Prostaglandinen stimuliert. Bestimmte Prostaglandine (J2/15dJ2) stimulieren dann über ihren Rezeptor (PPARgamma) das Fibroblastenwachstum, eine Voraussetzung für die Fibrose. Diese Ergebnisse sind für krankhafte Bindegewebsumbauvorgänge und speziell für die Tubulusfibrose bei Spermatogenesedefekten von Bedeutung: Bei Spermatogenesedefekten fanden wir, daß Mastzellvermehrung und Aktivierung mit der Expression von COX-2 in interstitiellen Zellen einhergehen. Bei Hoden mit normaler Spermatogenese (und nur wenigen Mastzellen) war COX-2 dagegen nicht nachweisbar. Rezeptoren für Tryptase sind auf interstitiellen Zellen und relevante Prostaglandinrezeptoren auf peritubulären Zellen nachweisbar. Es ist demnach möglich, daß Mastzelltryptase COX-2- und Prostaglandinbildung im infertilen Hoden anregt und dies letztlich zur Fibrose in der Tubuluswand führt, eine Veränderung, die sicherlich zur Spermatogenesestörung beiträgt. Die Aufklärung des Signalweges der Tryptase erlaubt es erstmals auch, gezielt über eine Beeinflussung des Fibroseprozesses nachzudenken: Mastzellstabilisatoren, Antagonisten von Tryptase, von COX-2 oder PPARgamma bieten sich an.; Fibrotic thickening of the wall of the seminiferous tubules is a hallmark of male infertility, but neither causes nor the direct consequences of tubular fibrosis are known. Since male infertility is also associated with increased numbers of activated mast cells, we propose that secreted mast cell products may be involved in the pathogenesis of tubular fibrosis and possibly male infertility. Evidence for this hypothesis is derived from cell culture and ex-vivo experiments: We found that actions of the major mast cell product, tryptase, includes formation of COX2 and synthesis of prostaglandins in target cells. Prostaglandin J2/15dJ2, which act via their receptor (PPARgamma), are responsible for fibroblast proliferation, a prerequisite of fibrosis. This may be of relevance for fibrosis in general and for testicular tubular fibrosis in particular: We found COX2 in testes of infertile men, but not of men with normal spermatogenesis, implying formation and action of prostaglandins. Since peritubular cells bear PPARgamma and since activated mast cells are at least tripled in infertile men, we propose a chain of events initiated by mast cell tryptase eventually leading to tubular fibrosis. Since tubular fibrosis is likely to be involved in the process leading to the damage of spermatogenesis, these results may pinpoint new targets for possible therapeutic interventions: mast cells, tryptase, COX2 and prostaglandins, as well as PPARgamma.

Description of the last larval instar and pupa of Aspisoma fenestrata Blanchard, 1839 (Coleoptera: Lampyridae) with brief notes on its biology

Description of the last larval instar and pupa of Aspisoma fenestrata Blanchard, 1839 (Coleoptera: Lampyridae) with brief notes on its biology Archangelsky, Miguel The last instar larva and pupa of Aspisoma fenestrata are described and figured for the first time. Notes for comparison with two other unidentified Aspisoma larvae are provided, as well as brief notes on the biology of A. fenestrata. Comparison of Aspisoma larvae with other known Cratomorphini larvae places Aspisoma closer to Pyractomena than to Cratomorphus.

Percolation of polyatomic species on square lattices

Percolation of polyatomic species on square lattices Cornette, Valeria Cecilia; Ramirez Pastor, Antonio Jose; Nieto Quintas, Felix Daniel In this paper, the percolation of (a) linear segments of size k and(b) k-mers of different structures and forms deposited on a square lattice have been studied. In the latter case, site and bond percolation have been examined. The analysis of results obtained by using finite size scaling theory is performed in order to test the universality of the problem by determining the numerical values of the critical exponents of the phase transition occurring in the system. It is also determined that the percolation threshold exhibits a exponentially decreasing function when it is plotted as a function of the k-mer size. The characteristic parameters of that function are dependent not only on the form and structure of the k-mers but also on the properties of the lattice where they are deposited.

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